The purpose of the proposed project is to examine polyphenolic constituents from edible plants for their potential to prevent cancer and coronary heart disease. Epidemiological studies suggest that diets rich in certain plants may help to prevent these diseases. Considerable evidence indicates that plant polyphenolic constituents are responsible for much of these beneficial health effects. We are currently studying the polyphenolic constituents of a group of lesser-used tropical fruits for their cardioprotective properties. We propose expand these studies by looking at the polyphenolic constituents of 11 additional species. We have selected these species from four plant families, Sapotaceae, Clusiaceae, Sterculiaceae, and Rananculaceae, based on a combination of chemotaxonomy, ethonobotanical uses, and initial antioxidant testing. We have done extensive literature reviews for dereplication. Based on chemotaxonomy, we anticipate obtaining a group of structurally diverse polyphenolic constituents from these 11 species. Polyphenolic constituents will be isolated using activity-guided fractionation employing a chemical assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH). The polyphenols will be purified using a variety of chromatographic techniques, and the compounds will be identified using one- and two-dimensional nuclear magnetic resonance and other spectroscopic methods. The purified polyphenols will be prioritized for further study based on uniqueness of chemical structure and potency of antioxidant activity in the DPPH assay. Selected polyphenols will be tested in mechanism-based in vitro assays to assess their cardioprotective and cancer chemopreventive activities. A low-density lipoprotein oxidation assay will be used to assess the cardioprotective properties of the polyphenols. We will also examine the ability of the polyphenols to inhibit the activity of the epidermal growth factor receptor (EGFR) and exert other cytotoxic effects on cell lines that overexpress EGFR, including colon cancer, breast cancer, and squamous carcinoma cells. We anticipate that the proposed research will lead to the discovery of novel polyphenols with specific mechanisms of actions. These compounds may serve as models for new therapeutic agents for the treatment and/or prevention of cancer and hypercholesterolemia.